Rotation or Change of Biotherapy After TNF Blocker Treatment Failure for Axial Spondyloarthritis (ROC-SPA)

November 15, 2024 updated by: Centre Hospitalier Universitaire de Saint Etienne

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by inflammatory arthritis and enthesitis involving the spine. AxSpA prevalence is around 0.17% of the French population. Tumor necrosis factor (TNF) was the first target defined in axSpA. Since one third of axSpA patients failed to the first TNF blocker, many axSpA patients received a second biological Disease-Modifying AntiRheumatic Drugs (bDMARDs). Until few months, the only choice was to use a second TNF blocker.Since 2003, pharmaceutical companies investigated efficacy of TNF blockers already used in rheumatoid arthritis. Etanercept is a fusion protein with TNF receptor type II p75 and IgG1 Fc fragment, whereas adalimumab, infliximab, and golimumab are monoclonal antibodies. Certolizumab is a fusion between a fab fragment targeting TNF and a Peg fraction. All demonstrated efficacy versus placebo in a randomized double blinded study

In case of failure to the first TNF blockers, rheumatologists will follow the "Treat-to-Target" principle. This approach already demonstrated its benefit in rheumatoid arthritis or in psoriatic arthritis. This concept was also suggested for axSpA with low levels of evidence and recommendation. So rheumatologist will provide the best treatment in case of failure to the first TNF blockers, which is a daily clinical situation. Since few months, rheumatologists have the choice between targeting IL-23/17 axis compared to a second TNF blocker.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Angers, France
        • CHU d'Angers
      • Besançon, France
        • CHRU Besançon
      • Bobigny, France
        • APHP- Hôpital Avicenne
      • Bordeau, France
        • Chu Bordeaux
      • Brest, France
        • CHRU Brest
      • Clermont-Ferrand, France
        • Chu Clermont-Ferrand
      • Grenoble, France
        • CHU de Grenoble Alpes
      • La Roche-sur-Yon, France
        • CHD Vendee
      • Le Mans, France
        • CH Le mans
      • Lille, France
        • CHRU Lille
      • Lomme, France
        • Hôpital Saint-Philibert
      • Lyon, France
        • Hopital Edouard Herriot
      • Lyon, France
        • CH Lyon Sud
      • Montpellier, France
        • CHRU Montpellier
      • Montpellier, France
        • CHU Montpellier - 2 - Unité Clinique thérapeutique des Maladies Ostéo-Articulaires
      • Nancy, France
        • CHU Nancy
      • Nantes, France
        • CHU de Nantes
      • Nice, France
        • CHU de Nice
      • Orléans, France
        • CHR d'Orléans
      • Paris, France
        • APHP - Hopital Cochin
      • Paris, France
        • APHP - Hopital Bichat
      • Paris, France
        • APHP - Hôpital Saint-Antoine
      • Paris, France
        • APHP - Kremlin-Bicêtre
      • Paris, France
        • APHP - Hopital Ambroise Pare
      • Paris, France
        • APHP - Hôpital Henri Mondor
      • Paris, France
        • APHP - Hôpital Lariboisière
      • Paris, France
        • APHP - hôpital Pitié-Salpêtrière
      • Poitiers, France
        • Chu de Poitiers
      • Reims, France
        • Chu Reims
      • Rouen, France
        • CHU de ROUEN
      • Saint-Étienne, France, 42055
        • CHU Saint-Etienne
      • Strasbourg, France, 67200
        • CHU Strasbourg - Hautepierre
      • Toulouse, France
        • CHU Toulouse
      • Tours, France
        • CHRU Tours
  • Monaco
      • Monaco, Monaco
        • CH Princesse de Grace

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Active axSPA with BASDAI>4 or ASDAS>3.5, who need change in TNF blocker treatment
  • Aged over 18 years
  • Inadequate response after at least 3 months to the 1st TNF blocker
  • If non biologic DMARD treatment : stable dose for at least on month before inclusion
  • If oral corticosteroids treatment : stable dose for at least on month before inclusion
  • If NSAIDs treatment : stable dose for at least on month before inclusion
  • Ability to complete questionnaires
  • Social security affiliation
  • Informed written consent given

Exclusion Criteria:

  • Any contra-indication to TNF blocker and/or secukinumab
  • Inflammatory bowel diseases
  • Existing pregnancy, lactation, or intended pregnancy within the next 15 months Active tuberculosis or other severe infections such as sepsis or opportunistic infections
  • Active infections, including chronic or localised infections.
  • Moderate to severe heart failure (NYHA classes III/IV)
  • Impossibility to give informed consent
  • Impossibility to be followed for 12 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: targeting IL-23/17 axis

The experimental group (targeting IL-23/17 axis) receiving secukinumab in compliance with the marketing authorization regimen: 150 mg per week for 5 weeks, and then every month by subcutaneous injection.

Blood specimen at each visits
Drug: Secukinumab
Secukinumab : 150 mg per week for 5 weeks, and then every month by subcutaneous injection
Biological: blood specimen
Blood specimen at each visits for measurement of bDMARS blockers concentration and anti-drug antibody concentration
Active Comparator: TNF blocker

• The control group receiving a second TNF blocker in compliance with the marketing authorization regimen:

The TNF blocker (originator or biosimilar) will be different to the TNF used before the inclusion and will be chose by the investigator:

  • infliximab: 5mg/kg per IV infusion at weeks 0, 2, 6, and then every 6 weeks,
  • etanercept: 50mg per week in subcutaneous injection,
  • adalimumab: 40mg every other week in subcutaneous injection,
  • certolizumab: 400mg every other week 3 times, and then 200mg every other week or 400mg per month in subcutaneous injections,
  • golimumab: 50mg every month in subcutaneous injection, in case of overweight (>100kg) an inadequate response, 100mg every month is allow.

Blood specimen at each visits
Biological: blood specimen
Blood specimen at each visits for measurement of bDMARS blockers concentration and anti-drug antibody concentration
Drug: TNF blocker

TNF blocker (originator or biosimilar) :

  • infliximab: 5mg/kg per IV infusion at weeks 0, 2, 6, and then every 6 weeks,
  • etanercept: 50mg per week in subcutaneous injection,
  • adalimumab: 40mg every other week in subcutaneous injection,
  • certolizumab: 400mg every other week 3 times, and then 200mg every other week or 400mg per month in subcutaneous injections,
  • golimumab: 50mg every month in subcutaneous injection, in case of overweight (>100kg) an inadequate response, 100mg every month is allow.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of axSpA patients with a clinical response Assessments in Ankylosing Spondylitis International Society 40 (ASAS 40) at week 24
Time Frame: 24 weks

ASAS 40 is defined as an improvement of at least 40% and absolute improvement of at least 2 units on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion:

  • Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."
  • Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."
  • Function : BASFI average of 10 questions measured by numerical rating scale with extremes labelled "easy" and "impossible."
  • Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening at all in remaining domain
24 weks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of axSpA patients with a clinical response ASAS 40 at week 12
Time Frame: 12 weeks

ASAS 40 is defined as an improvement of at least 40% and absolute improvement of at least 2 units on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion:

  • Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."
  • Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."
  • Function : BASFI average of 10 questions measured by numerical rating scale with extremes labelled "easy" and "impossible."
  • Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening at all in remaining domain
12 weeks
Proportion of axSpA patients with a clinical response ASAS 40 at week 52
Time Frame: 52 weeks

ASAS 40 is defined as an improvement of at least 40% and absolute improvement of at least 2 units on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion:

  • Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."
  • Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."
  • Function : BASFI average of 10 questions measured by numerical rating scale with extremes labelled "easy" and "impossible."
  • Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening at all in remaining domain
52 weeks
Proportion of axSpA patients with a clinical response ASAS 20 at week 12
Time Frame: 52 weeks

ASAS 20 is defined as an improvement of at least 20% and absolute improvement of at least 1 unit on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion:

  • Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."
  • Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."
  • Function : BASFI average of 10 questions regarding measured by numerical rating scale with extremes labelled "easy" and "impossible."
  • Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening in a similar amount in the fourth domain
52 weeks
Proportion of axSpA patients with a clinical response ASAS 20 at week 24
Time Frame: 24 weeks

ASAS 20 is defined as an improvement of at least 20% and absolute improvement of at least 1 unit on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion:

  • Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."
  • Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."
  • Function : BASFI average of 10 questions regarding measured by numerical rating scale with extremes labelled "easy" and "impossible."
  • Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening in a similar amount in the fourth domain
24 weeks
Proportion of axSpA patients with a clinical response ASAS20 at week 52
Time Frame: 52 weeks

ASAS 20 is defined as an improvement of at least 20% and absolute improvement of at least 1 unit on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion:

  • Patient global assessment : numerical rating scale with extremes labelled "none" and "severe."
  • Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."
  • Function : BASFI average of 10 questions regarding measured by numerical rating scale with extremes labelled "easy" and "impossible."
  • Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening in a similar amount in the fourth domain
52 weeks
Proportion of axSpA patients with a partial remission rate at week 12
Time Frame: 12 weeks

Partial remission is defined by values lower than 2/10 in each 4 domains:

  • Patient global assessment measured on a numerical rating scale with extremes labelled "none" and "severe."
  • Pain assessment represented by the average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."
  • Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by numerical rating scale with extremes labelled "easy" and "impossible."
  • Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI regarding morning stiffness as measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours."
12 weeks
Proportion of axSpA patients with a partial remission rate at week 24
Time Frame: 24 weeks

Partial remission is defined by values lower than 2/10 in each 4 domains:

  • Patient global assessment measured on a numerical rating scale with extremes labelled "none" and "severe."
  • Pain assessment represented by the average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."
  • Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by numerical rating scale with extremes labelled "easy" and "impossible."
  • Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI regarding morning stiffness as measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours."
24 weeks
Proportion of axSpA patients with a partial remission rate at week 52
Time Frame: 52 weeks

Partial remission is defined by values lower than 2/10 in each 4 domains:

  • Patient global assessment measured on a numerical rating scale with extremes labelled "none" and "severe."
  • Pain assessment represented by the average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain."
  • Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by numerical rating scale with extremes labelled "easy" and "impossible."
  • Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI regarding morning stiffness as measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours."
52 weeks
Proportion of axSpA patients with a ASDAS major improvement at week 12
Time Frame: 12 weeks
ASDAS major improvement was defined by a variation of ASDAS-CRP≥2
12 weeks
Proportion of axSpA patients with a ASDAS major improvement at week 24
Time Frame: 24 weeks
ASDAS major improvement was defined by a variation of ASDAS-CRP≥2
24 weeks
Proportion of axSpA patients with a ASDAS major improvement at week 52
Time Frame: 52 weeks
ASDAS major improvement was defined by a variation of ASDAS-CRP≥2
52 weeks
Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 12
Time Frame: 12 weeks
Patient with the same bDAMRs treatment at inclusion and week 12
12 weeks
Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 24
Time Frame: 24 weeks
Patient with the same biological Disease-Modifying AntiRheumatic Drug (bDAMR) treatment at inclusion and week 24
24 weeks
Proportion of axSpA patients with bDMARDs treatment at week 52
Time Frame: 52 weeks
Patient with the same biological Disease-Modifying AntiRheumatic Drug (bDAMR) treatment at inclusion and week 52
52 weeks
Number of adverse events
Time Frame: 52 weeks
Number of adverse events
52 weeks
Correlation between concentration of antibodies to bDMARS blockers and clinical response according to treatment
Time Frame: From baseline to 52 weeks
Concentration of antibodies to bDMARS blockers is measured by Enzyme Linked ImmunoSorbent Assay (ELISA) low disease activity is defined by BASDAI <4 and ASDAS <2.1
From baseline to 52 weeks
Correlation between concentration of anti-drug antibodies and clinical response according to treatment
Time Frame: From baseline to 52 weeks
Concentration of anti-drug antibodies is measured by Enzyme Linked ImmunoSorbent Assay (ELISA) low disease activity is defined by BASDAI <4 and ASDAS <2.1
From baseline to 52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre Hospitalier Universitaire de Saint Etienne

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ministry of Health, France

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Hubert MAROTTE, MD, CHU Saint-Etienne

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 14, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 21, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 20, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 20, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 26, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 18, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1608185
  • 2017-004700-22 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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